The objectives of the proposed research are to provide a detailed description of the mechanisms by which organic ions are secreted by the kidney. Since secretion is a transepithelial phenomenon, the approach selected is to study membrane transport in plasma membrane vesicles isolated from both faces of the renal cell. Our previous work demonstrated that "specifically-mediated" transport of both organic anions and organic cations occurred in both the basolateral and brush border membranes, and gave information on the relative contributions of the two membranes to the overall process. The present studies are designed to describe the underlying molecular mechanisms and to explain the energetics. Supposedly, they are "secondarily-active" transport mechanisms. Another objective is to compare the transporters located in either membrane on the basis of mechanism, chemical properties, and immunological cross reactivity. A third objective is to examine some amphoteric drugs to determine if they behave as anions or cations. A fourth objective is to isolate the transporters from both membranes in order to relate structure and function. The long-range goal is to understand the molecular mechanisms involved in secretion and to understand how secretion is regulated and controlled by the renal cell.